EFFECT OF FLUCONAZOLE ON VIABILITY OF CANDIDA-ALBICANS OVER EXTENDED PERIODS OF TIME

The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time, It is possible tha t an azole antifungal drug such as fluconazole, with primarily fungist atic activity in standard in vitro susceptibility tests,might be able to damage the fungal cells and reduce their viability over prolonged i ncubations under nonproliferating conditions, To test this possibility , Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degree s C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times duri ng this period revealed no increased loss of viability for the flucona zole-exposed organisms, However, when fluconazole was added to the org anisms maintained in distilled water (with or without pretreatment wit h the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were fou nd for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 mu g of fluconazole per mi versus 0 of 10 and 1 of 11 control samples (P o f <0.01 and 0.001, respectively), The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C r ather than 25 degrees C, These findings suggest that fluconazole may h ave fungicidal effects on fungal cells during prolonged exposures unde r conditions in which the organisms are prevented from proliferating b y lack of nutrients.